Abstract: AIM: To develop a UPLC-MS/MS method to determine the concentration of tamoxifen and its metabolites in human plasma and application. METHODS: The equipments were Waters AcQuity ultra-high performance liquid chromatography with API4000 type triple quadrupole mass spectrometer , Thermo Hypurity C₁₈ column (150 mm×2.1 mm, 5 μm) was used in the experiment.10 mmol/L ammonium formate-acetonitrile(40∶60, V/V) was used as mobile phase and the flow rate was 0.3 mL/min, the injection volume was 10 μL, the column temperature was 30 ℃ and the sample room temperature was set at 5 ℃.The concentrations of tamoxifen and its metabolites were monitored by Mass with ESI source in positive ion mode and multiple reaction monitoring (MRM) way. RESULTS: Solid phase extraction method was used for sample preparation, tamoxifen, ND-Tam and TamNox were linear range from 1-400 ng/mL, 4-OH-Tam and 4-OHND-Tam were linear range from 0.4-160 ng/mL and 2-800 ng/mL respectively, the limitation of tamoxifen and its metabolites were about 1-2 ng/mL, some even less than 0.4 ng/mL,the method was high sensitivity, stability and specificity and has already been used for determination of tamoxifen and its metabolites in human successfully. CONCLUSION: The method is simple, accurate, repetitive for the determination of tamoxifen and its metabolites in human plasma and suitable for the concentration monitoring in clinic, present study also provide technical method for pharmacogenetics research.

Key words: Tamoxifen, UPLC-MS/MS, CYP3A4